Patterns of expression of Bax, Bcl-2 and Bcl-x(L) in the implantation site in rat during pregnancy

The uterine endometrium responds to blastocyst implantation with extensive proliferation and differentiation of stromal cells into decidual cells, forming the antimesometrial and mesometrial decidua. These undergo regression by apoptosis but as this process occurs at different time periods suggest that there is spatially dependent temporal control of apoptosis in these specific regions. To elucidate the role of the mitochondrion-dependent signalling pathway in tissue regression, we investigated the spatial and temporal pattern of expression of the Bcl-2 family members in uterine tissues of the implantation site, from the post-implantation period to parturition. Furthermore, the activities of the initiator caspases-8 and -9, and of the executioner caspase-3 were determined. Overall Bax and Bcl-2 were expressed from day 8 till day 19, whilst Bcl-x(L) was extinguished by day 16. In the antimesometrial and in the mesometrial decidua both Bcl-2 and Bax declined from days 10 to 12. In the latter Bcl-2 immunoreactivity decreased till the end of pregnancy, whilst for Bax a constant level remained thereafter. The pattern of variation of enzymatic activities throughout pregnancy for all the enzymes was similar, increasing from days 10 to 14 and decreasing towards the end of pregnancy. The increased levels of active caspase-9 correlated with Bax/Bcl-2 and Bcl-x(L) expression suggesting that the apoptotic mitochondrion-dependent pathway is involved in decidual regression during pregnancy progression.     

Immunopathologic study of the implantation site in molar pregnancy

The implantation sites of 11 molar pregnancies were examined for the deposition of immunoglobulin and complemented by direct immunofluorescence. None of the 10 women experiencing their first molar pregnancy had immunoglobulin or complement deposition in the implantation site. The one patient with immunoglobulin and complement deposition in the implantation site was aslo the only patient experiencing a second molar pregnancy. Immunofluorescent staining for IgG, IgM, and C3 was confirmed to the decidual arteries in this patient and was unassociated with endovascular trophoblastic deposits. While only one of the 10 women with their first molar pregnancy had focal vasculitis at the implantation site, the patient with her second consecutive mole had diffuse vasculitis. Because molar implantation sites are generally free of immunoglobulin and complement deposition, molar pregnancies do not appear to induce a vigorous host humoral immune response at the time of presentation at the molar implantation site.     

Patterns of growth of uterine leiomyomas during pregnancy. A prospective longitudinal study

In a prospective study 32 leiomyomas (fibroids) in 29 pregnant women were examined with ultrasound every 3-8 weeks. Each patient had between 3 and 6 scans (mean 4.4) during the course of pregnancy, and 13 patients had a final scan at 6 weeks postpartum. An individual growth curve was established for each tumour and the patterns of growth were analysed. No increase in size during the pregnancy was observed in 25 fibroids (78%). Only 7 (22%) increased in size but by no more than 25% of the initial volume. At 6 weeks postpartum the size of the fibroids did not differ significantly from the size during pregnancy.     

Patterns of growth of uterine leiomyomas during pregnancy. A prospective longitudinal study

Summary. In a prospective study 32 leiomyomas (fibroids) in 29 pregnant women were examined with ultrasound every 3–8 weeks. Each patient had hetween 3 and 6 scans (mean 4.4) during the course of pregnancy, and 13 patients had a final scan at 6 weeks postpartum. An individual growth curve was established for each tumour and the patterns of growth were analysed. No increase in size during the pregnancy was observed in 25 fibroids (78%). Only 7 (22%) increased in size but by no more than 25% of the initial volume. At 4 weeks postpartum the size of the fibroids did not differ significantly from the size during pregnancy.     

子宫肌瘤细胞凋亡及增殖状况研究

目的 探讨细胞凋亡与凋亡调控基因在子宫肌瘤的发生、发展中的作用。方法 2000～2001年应用原位末端脱氧核苷酸转移酶标记(terminal deoxynucleotity transferase mediated dUTP nick end labeling,TUNEL)技术和免疫组织化学染色观察子宫肌瘤和正常子宫肌层组织中细胞凋亡和凋亡调控基因增殖细胞核抗原(PCNA的表达。结果 子宫肌瘤组织中细胞凋亡指数显著高于正常子宫肌层组织(P<0.01)。子宫肌瘤组织中PCNA蛋白阳性率高于正常子宫肌层组织(P<0.01)。凋亡细胞多分布在PCNA蛋白阴性区,阳性区仅有少量分布,且PCNA阴性区细胞凋亡指数高于阳性区。结论 细胞凋亡失控在子宫肌瘤生成过程中起重要作用,PCNA蛋白表达能比较准确地反映子宫平滑肌瘤的细胞增殖信息,子宫肌瘤的发生与增殖和(或)凋亡失衡密切相关。     

Impact of experimental diabetes on the maternal uterine vascular remodeling during rat pregnancy

Normal pregnancy is associated with an increase in uteroplacental blood flow in part due to growth and remodeling of the maternal uterine vasculature. In this study, we characterized the effect of diabetic pregnancy on vascular growth of the maternal uterine vasculature and on the passive mechanical properties of the uterine resistance arteries. Diabetes was induced in pregnant rats by injection of streptozotocin and confirmed by development of hyperglycemia. Fetuses of diabetic rats were significantly smaller and placentas larger compared to controls. Pregnancy-induced axial elongation of the mesometrial uterine vasculature was not altered by diabetes. Vascular wall thickness was unchanged between groups. Wall distensibility was increased and the rate constant of an exponential function fitted to stress-strain curve was significantly reduced demonstrating decreased wall stiffness in diabetic uterine radial arteries compared to controls. We conclude that experimental diabetes in rat pregnancy does not compromise the growth of maternal uterine vasculature but alters passive mechanical properties of the uterine radial arteries.     

Carcinoma of the uterine cervix during pregnancy

Pregnancy offers a unique opportunity for the early diagnosis of cervical cancer, due to the fact that pregnant patients have many possibilities of gynecological and cytological examinations. There is much evidence that pregnant women have two to three-fold higher chance of having preneoplastic lesions and early, operable stages of disease diagnosed. The preneoplastic lesions do not require any intervention during pregnancy. However, precise, serial colposcopic examinations, completed by biopsy if necessary, must be seriously considered in order to exclude invasive cancer. The only indication for conization during pregnancy is to rule out or confirm microinvasive or invasive cancer, provided such diagnose can change the time and the way of delivery. Invasive cervical cancer diagnose is frequently associated with difficult medical and ethical decisions. The most proper approach should be considered, taking into account the benefit of the mother and the child. The decision is easier in the early stage of cancer, because it has been proven that six- to twelve-week delay of the beginning of the therapy does not deteriorate the cancer outcome but it enables the fetus to acquire sufficient lung maturity. Advanced carcinoma of the cervix forces us to take prompt therapeutic decisions. Both, the continuation of the pregnancy and the administration of neoadjuvant chemotherapy are still possible.     

Genetic control of uterine receptivity during implantation

Implantation involves complex molecular interactions between implanting blastocysts and the hormonally primed uterus. Gene targeting allows the generation of mice lacking a specific gene or genes and has proved to be of considerable value when combined with classical physiology in understanding many biological questions, such as the process of implantation. In this article, we review genes that have been demonstrated by gene targeting in mice to be required in the uterus for implantation. In particular, we focus on a specific class of developmental control genes, the mammalian Hox genes, and their role in this process. Lastly, we attempt to synthesize current knowledge about the genetic control of implantation and to build a working genetic model for the implantation pathway.     

Structural remodeling of rat uterine veins in pregnancy

OBJECTIVE: This study characterized the cellular remodeling that contributes to uterine venous growth during gestation and evaluated the effect of pregnancy on the mechanical properties of the uterine vein. STUDY DESIGN: Diameter and distensibility were calculated in pressurized uterine veins from virgin and pregnant (19-20 days of gestation) rats; the rates of cellular division (endothelial, vascular smooth muscle) were quantified with an intraperitoneal bromodeoxyuridine injection and immunohistochemistry. Elastin content, adrenergic nerve density, and wall thickness were determined in fixed uterine veins and quantified with an imaging program. RESULTS: There was a statistically significant increase in the diameter and mitotic indices (endothelial, vascular smooth muscle) in uterine veins from late pregnant versus nonpregnant animals. Adrenergic nerve density was diminished significantly during gestation. Venous distensibility increased during pregnancy, with an associated reduction in elastin content. CONCLUSION: Pregnancy results in coordinated and multifaceted structural remodeling of uterine veins with subsequent changes in caliber, mechanical properties, rates of cellular division, adrenergic innervation, and matrix composition.     

Cyclic AMP and cyclic GMP in the implantation site of the rat

Endometrial differentiation of the implantation site (IS) is regulated by hormonal and local influences (egg). To better understand the possible participation of cyclic nucleotides in this process, we measured cAMP and cGMP by RIA in IS of the rat on day 6 of pregnancy. IS showed an increase of both nucleotides (3.54 and 0.57 pmoles/mg DNA) when compared with the remaining endometrium (NIS) (2.70 and 0.30). The cAMP/cGMP ratio did not change significantly. We also found an increase in the proteins/mg DNA ratio (12.04 in IS vs 10.63 in NIS) and in the hydration of IS. Our hypothesis is that together these two nucleotides function as a monodirectional system in which they act cooperatively as positive effectors of different sequential steps in the overall process of implantation.     

Local versus systemic influences on uterine vascular reactivity during pregnancy in the single-horn gravid rat

This study was conducted to determine whether gestational changes in maternal uterine artery reactivity are primarily driven by local vs. systemic factors. Rats underwent surgical ligation of one oviduct, thereby restricting implantation and pregnancy to one uterine horn while maintaining a gestational endocrine milieu. Uterine arcuate arteries were isolated and cannulated to evaluate reactivity. Vessels from the implanted horn were significantly more sensitive to phenylephrine and less sensitive to sodium nitroprusside than those from the non-implanted horn; endothelial basal calcium levels were only increased in the implanted horn. Conversely, there were no differences in sensitivity to acetylcholine, or its effects on endothelial cell calcium, although efficacy was greater in vessels from the implanted vs. non-implanted horn. These findings demonstrate that local factors are predominant in inducing changes in vascular smooth muscle function, while endothelial adaptations result from an interplay between local and systemic factors, with distinct effects attributable to each.     

Changes in uterine myoma dimentions during pregnancy

The purpose of this study is to follow up the changes in the myoma dimentions during pregnancy (1st, 2nd and 3rd trimester). The study is prospective and includes 90 pregnant women with myoma during the period 2002-2006. If more than one myoma was diagnosed, the largest one was considered to be representative. Our data show that the combination of myoma and pregnancy is more frequent with women over the age of 30 and it is more frequent with nullipares (63.2%). Single myomas were more frequent with 58%, 48% of the myomas were intramural and 62% were located in the uterine corpus. Our study shows that during the first trimester there is no change in the myomas dimentions in 35%-43% of the cases and during the second trimester there is no change of the myona dimentions in 50% of the cases. During the third trimester there are only 5% of the myomas that change their dimentions. We conclude, that the myomas, that enlarge during the first trimester, usually enlarge during the second trimester as well. We found no decrease of the myoma dimentions during the third trimester.     

Surgical emergencies of the uterine adnexae during pregnancy

During the 5-year period 1976-1980, seven cases of emergent surgical disease of the adnexae during pregnancy were encountered. The incidence of 1:1832 deliveries approximated that of appendicitis (1:1603 deliveries) during the same period. There were three cases of adnexal torsion, two ruptured ovarian cysts with hemorrhage, one heterotopic pregnancy, and one ruptured endometrioma. The right side was more commonly the site of the pathology, and abdominal pain the only consistent presenting symptom. Fever, tachycardia, and leukocytosis were inconsistent findings. Culdocentesis was positive in two cases. Four desired pregnancies were carried successfully to term postoperatively. Surgical emergencies of the adnexae will be encountered during pregnancy more commonly than is generally recognized. Aspects of obstetric management are described. If prompt surgical intervention is undertaken in pregnancy when the clinical picture suggests an acute abdomen, a satisfactory outcome can be expected.